ABSTRACT
Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression.1 Corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA/stress system. CRH is a peptide of 41 amino acid residues, originally discovered and sequenced by Vale et al,2 which is produced in the medial parvicellular neurones of the paraventricular nucleus of the hypothalamus. These neurones project to the external zone of the median eminence, where CRH is released into the portal vasculature to act on CRH1 receptors at the anterior pituitary. CRH and AVP act synergistically in bringing about adrenocorticotrophin (ACTH) release from the corticotrophs of the anterior pituitary which in turn stimulates cortisol output from the adrenal cortex. Following its identification in 1954, vasopressin, a nonapeptide, was considered the principal factor in the regulation of ACTH release but, with the subsequent elucidation of the structure of CRH and the domination of the one neurone/one transmitter principle, the role of CRH came to overshadow that of AVP. This dominance has been reflected in neuroendocrine studies conducted in depression.
